Saturday, April 16, 2011

Our addiction to antibiotics created the superbug

In the December 2009 edition of Antimicrobials and Chemotherapy, an article carried the lines: "A Swedish patient of Indian origin travelled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain." But it was the next line that really caught the attention of the microbiological and infectious disease fraternity: "The isolate, Klebsiella pneumoniae 05-506, was shown to possess a metallo-├čbeta-lactamase (MBL) but was negative for previously known MBL genes."

Of course, beta lactamases are hardly exotic, in fact they traipse around hospital wards with the wild abandon only a microscopic marvel of evolution can exude. But this one, initially named New Delhi Metallo (NDM) beta lactamase (the name has since been changed to Plasmid-encoding Carbapenemase-resistant Metallo-B-Lactamase), was different. This one refused to be put down under the jackboots of modern antibiotics. This one was a fighter. And initial findings suggested it was born and brought up right here in India.

But as news cycles grow and collapse in a rapid sequence, NDM-1 disappeared off the news and into the gaping hole of not-quite-there superbugs. And it stayed there till the April edition of the medical journal Lancet came out.

In their paper Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study, Messrs Walks, Weeks, Livermore, and Toleman, wrote: ‘Not all patients infected with NDM-1-positive bacteria have a history of hospital admission in India, and extended-spectrum -lactamases are known to be circulating in the Indian community. We therefore measured the prevalence of the NDM-1 gene in drinking water and seepage samples in New Delhi.’

They found bacteria with the PCM gene in drinking water and seepage samples in New Delhi. 50 tap water samples and 171 seepage samples were collected from sites within 12 km of central New Delhi. Of these samples, 20 strains of bacteria were found to contain PCM gene in 51 out of 171 seepage samples and 2 out of 50 tap water samples.

If this was a Hollywood movie, it's about now one would have turned to the rest of the group and said: "Gentlemen, I think we'll need a bigger dose of antibiotics."

But to the lay reader, biological acronyms tend to hover meaninglessly in the air, until that is, they hit home. So is NDM-1 the superbug that's going to make the Spanish Flu look like a particularly bad case of the sniffles?

Is it going to make antibiotics redundant? And more importantly, from a historical perspective, did we give it to the world?

The initial reaction to the Lancet findings were apocalyptic to say the least. "The superbug is out of hospitals and on the street", "It's in the water supply and in your home", were just a few of the doomsayers threats.

That naturally led to the conspiracy theorists feeling left out: "It's a Western conspiracy to dent India's nascent health tourism sector", "It's meant to belittle our sanitation facilities"....

Unfortunately for headline writers across the country, the truth may not be all that dramatic.
Bacteriologists argue that beta lactamases have been in existence around the world for years. They were triggered through our abuse of antibiotics.

Beta lactamase is an enzyme released by certain bacteria. This enzyme is capable of crossing over to other bacterial species. And when this happens, an otherwise relatively harmless bacteria becomes a powerful organism or 'superbug'. In short, a superbug does not respond to ordinary antibiotics.
Even elite antibiotics often fail to kill superbugs.

The problem is, NDM-1 has ideas above its of them is that it wants to be a 'superbug'.
The Central government has launched its own study that will confirm or debunk the Lancet's version. But it remains a fact that antibiotic abuse is a problem in India. India has the dubious distinction of being a nation that consumes the highest quantity of antibiotics. Then there's the issue of sanitation, or the lack thereof. Hospital ICUs are colonised by bacteria that are capable of using antibiotics like penicillin as nutrition. Although our municipal authorities claim to test the water regularly, do they have the mechanism to find out whether the bacteria are carrying the superbug gene, NDM-1, or any beta lactamase enzyme.

In the absence of sophisticated culture tests, it will never be known if the water we drink is contaminated by simple bacteria or superbugs. Then there's the issue of abuse of antibiotics in the veterinary sciences. Dairy milk and meat have been found to be contaminated by antibiotic residue. Animal hormones are used for artificial ripening and increasing the size and texture of fruit like mangos, bananas and papaya.

The abuse of antibiotics, scientists cite, is one of the contributory factors for the emergence of superbugs. "There should be checks on the use of broad spectrum antibiotics. Doctors often prescribe broad spectrum antibiotics for problems that require just pathogen-specific antibiotics. And that makes his body resistant to antibiotics. In a way we are responsible for the emergence of superbugs," says senior geneticist, Dr M.N. Khaja.

Unfortunately, due to lack of updated medical knowledge and regular Continuing Medical Education (CME) courses, many doctors fail to recognise the problem when patients approach them for medical help. Medical knowledge is undergoing a sea change thanks to the discovery of new pathogens, changes in the way diseases manifest, and the emergence of drug-resistant ailments.

The Medical Council of India had long-ago proposed holding regular refresher courses for doctors to keep them abreast of developments in the medical world. It had also proposed that only those who attend the refresher course and pass the examination conducted after the course will be eligible for re-registration. But these proposals have been kept in cold storage and many doctors are not informed of the advances in medical science.

"Updating medical knowledge should be made compulsory for doctors. It is worrying that 90 per cent of doctors do not know about new diseases like Crimean Congo Haemorrhagic Fever. When Chikungunya first broke out five years ago, doctors could not recognise it. Dengue has been around for many years, and yet doctors grapple with treatment. The trend is to first administer an antibiotic and if it does not work, change it. In this way doctors experiment with antibiotics and other medicines, indirectly giving birth to superbugs," says senior health activist, V. Satyanarayana.

The Central government has finally woken up to the problem of antibiotic abuse in the backdrop of Lancet's revelation, and is studying the need to bar the random sale of powerful antibiotics. If the Centre has its way, tertiary antibiotics will now be available to only a few important hospitals in the country. Some of the powerful drugs listed under Schedule H will be shifted to a new Schedule (Schedule H1).

General practitioners, small hospitals and the general public will not have access to these antibiotics. This will, to some extent, check the menace of over-the-counter sales of powerful medicines. Some scientists, however, believe that the Lancet study may be flawed. Did those involve in the Lancet study adopted a different yardstick when it came to discovering NDM-1? Indian scientists believe so.

Stating that the foecal-oral route of the transmission of enteric bacteria is not novel, Dr Niyaz Ahmed says it has always posed health risks for centuries, throughout the world. When these phenotypes are seen in Germany, Japan, China and Taiwan, Indian cities cannot remain exceptions.

However, the prevalence in the environment and in hospitals constitutes two different issues. Unfortunately, all the published reports on NDM-1, including the Lancet study, are based on 'convenience sampling'. "When conveniently spotted and potentially suspected sources are picked up as first choice and tested with highly sensitive tools such as Polymerase Chain Reaction (PCR) and Real Time PCR, it is possible to get positive results even in places such as Switzerland. However, culture or PCR positivity does not mean that a potential epidemic is brewing," he adds.

A senior scientist at the Centre for Cellular and Molecular Biology argues that had the Lancet team been sincere and really scientific in its approach, it would not have compared potable water from India and sewage water from Cardiff, Wales, for the NDM-1 study. "If they want to say sewage water in Europe is better than drinking water in India, it's a different story. But justice and fairness demands that the samples should be identical. They should have first compared Indian drinking water with drinking water samples from Europe, and then after ruling out the presence of NDM-1 in European water samples, they should have gone for sewage effluent sampling," the CCMB scientist said, on condition of anonymity.

But what are the implications of the superbug for you? According to senior physician Dr Aftab Ahmed, it will be a difficult task to treat health problems created by superbugs, as they do not respond even to powerful antibiotics. They, however, are susceptible to a couple of regimes. If these superbugs become resistant to these too, then it will be a Herculean task indeed. "If we do not kill Vibrio cholerae or E. coli in the stomach itself, it will spread to other parts of the body like blood, bones, lungs, heart and kidneys. Even simple diarrhoea caused by superbugs will become harder to treat," he warns.

Before we get lulled into a sense that this discussion has little value outside medical circles and peers looking for a review, here's a number to keep in mind: 100 million. That's the number of people that died of the Spanish Flu worldwide in 1918–19.


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